Original Contribution
The American Journal of Gastroenterology (2005) 100, 1317–1321; doi:10.1111/j.1572-0241.2005.41690.x
Effect of Rosiglitazone on Serum Liver Biochemistries in Diabetic Patients with Normal and Elevated Baseline Liver Enzymes
Naga Chalasani MD1, Evgenia Teal MS1 and Stephen D Hall PhD1
1Department of Medicine, Indiana University School of Medicine; The Regenstrief Institute for Health Care, Indianapolis, Indiana
Correspondence: Naga Chalasani, MD,, Indiana University School of Medicine, WD OPW 2005, 1001 West 10th Street, Indianapolis, IN 46202
Received 19 October 2004; Revised 0000; Accepted 3 January 2005.
Abstract
OBJECTIVES:
Thiazolidinediones (TZD) are recommended to be used cautiously in diabetics with mild elevations in liver enzymes and not to be used in those with alanine aminotransferase >2.5 upper limit normal (ULN). However, studies are not adequate that evaluated the risk of TZD hepatotoxicity in diabetics with elevated liver enzymes. We conducted a study to test if diabetics with elevated liver enzymes have increased risk for hepatotoxicity from rosiglitazone (only TZD available on our formulary).
METHODS:
This study consisted of two cohorts of patients prescribed rosiglitazone since January 2000. Cohort 1: 210 diabetics with elevated baseline liver enzymes (aspartate aminotransferase (AST) >40 IU/L and/or alanine aminotransferase (ALT) >35 IU/L) who received rosiglitazone, and cohort 2: 628 diabetics with normal liver enzymes who received rosiglitazone. Elevations in liver biochemistries over a 12-month period after initiating rosiglitazone were characterized into mild to moderate or severe elevations and into "Hy's rule" based on published criteria.
RESULTS:
Compared to cohort 2, patients in cohort 1 did not have higher incidence of mild to moderate (10%vs 6.6%, p= 0.2) or severe elevations (0.9%vs 0.6%, p= 0.9) in liver biochemistries. Similarly, the incidence of liver biochemistry abnormalities meeting the Hy's Rule was statistically not different between the two cohorts (0%vs 0.3%, p= 0.9). The frequency of discontinuing rosiglitazone therapy during the follow-up was similar between cohorts 1 and 2 (8.6%vs 8.1%, p= 1.0).
CONCLUSIONS:
These results suggest that diabetics with elevated baseline liver enzymes do not have a higher risk of hepatotoxicity from rosiglitazone than those with normal enzymes.
